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https://doi.org/10.1007/s10396-020-01030-w
Everything you need to know about ultrasound for diagnosis of gallbladder diseases
Abstract
Endoscopic ultrasonography (EUS) has excellent spatial resolution and allows more detailed examination than abdominal
ultrasonography (US) in terms of qualitative diagnosis of tumors and evaluation of tumor invasion depth. To understand the
role of EUS in gallbladder disease, we need to understand the normal gallbladder wall structure and how to visualize it on
EUS. In addition, gallbladder lesions can be classified into two broad categories: protuberant and wall-thickening lesions.
Here, the features on EUS were outlined. We also outlined the current status of EUS-FNA for gallbladder lesions as there
have been scattered reports of EUS-FNA in recent years.
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Accordingly, visualization of the cystic duct junction is it is important to make a thorough observation including
occasionally possible by continuing to advance the scope, the gallbladder fundus by visualizing successively from the
and visualization from the cystic duct to the gallbladder cystic duct toward the gallbladder neck.
neck is occasionally possible by rotating the scope (Fig. 4b).
However, as the direction of rotation at this point varies with iii) Contrast‑enhanced harmonic EUS
each patient, visualization should be performed while care-
fully following the cystic duct (Fig. 4c). Note that examina- Although contrast-enhanced harmonic EUS for gallbladder
tion of the entire gallbladder from within the stomach is not disease is not covered by health insurance, Choi et al. [3]
always possible. have reported that the presence of irregular intratumoral
In duodenal bulb scanning, the hilar hepatic ducts are vessels and a perfusion defect on contrast EUS can diag-
identified by visualizing the portal vein and tilting the scope nose gallbladder cancer in gallbladder polyps measuring at
downward while withdrawing it in counterclockwise rotation least 10 mm with a sensitivity and specificity of 93.5 and
(Fig. 5a). The cystic duct junction can be recognized through 93.2%, respectively (Fig. 6). Imazu et al. [4] also reported
this process (Fig. 5b). By rotating the scope while following that inhomogeneously enhanced patterns were observed in
the cystic duct, it is possible to visualize the whole gallblad- contrast EUS. However, further accumulation of knowledge
der from the neck to the fundus (Fig. 5c). As the direction is desired as there has been apparently no large-scale study
of rotation at this point also varies from patient to patient,
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on contrast-enhanced harmonic EUS in gallbladder diseases significance of treating lesions collectively as gallbladder
to date. polyps before a definitive diagnosis lies in the early detec-
tion of malignant disease from these lesions. Therefore,
3. Differential diagnosis of gallbladder lesions protuberant gallbladder lesions are first divided into neo-
plastic and non-neoplastic lesions. Differential diagnoses
Gallbladder lesions are broadly divided into protuber- such as adenomas or carcinomas for neoplastic lesions and
ant and wall-thickening lesions. Protuberant lesion is an cholesterol polyps, hyperplastic polyps, and gallbladder
inclusive category encompassing a variety of diseases, adenomyomatosis for non-neoplastic lesions are based on
both epithelial and non-epithelial, as well as benign and size, pedunculation, morphology, surface characteristics,
malignant diseases. It is a generic term for lesions that and internal echo. On the other hand, wall-thickening
have the specific morphological feature of forming a pro- lesions denote lesions in which the gallbladder wall is dif-
tuberance localized to the luminal side of the gallbladder fusely thickened. Differential diagnosis is made with ref-
[5]. In differentiating protuberant gallbladder lesions, the erence to the extent of wall thickening, surface structure,
classification of benign protuberant lesions by Christensen and presence or absence of Rokitansky–Aschoff sinuses
et al. is used [6]. However, from a clinical perspective, the (RAS).
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Ultrasonographic features of gallbladder protuberant punctiform foci reflecting cholesterolosis are visible [14]
lesions and gallbladder wall-thickening lesions are summa- (Fig. 7). Peduncles are thin and frequently unobserved even
rized in Tables. 1 and 2, respectively. on EUS.
When polyps reach ≥ 10 mm, epithelial hyperplas-
4. Protuberant lesions tic changes are reflected as lobulation, and internal echo
decreases, making differentiation from adenoma and early
i) Non‑neoplastic lesions (gallbladder polyps) gallbladder cancer difficult in some cases and necessitating
caution (Fig. 8).
Gallbladder polyps are small, localized, raised lesions B. Hyperplastic polyps: Hyperplastic polyps are classified
observed on the mucosal surface of the gallbladder. Histo- as proper epithelial or metaplastic epithelial polyps, and they
pathologically diverse diseases are included, whether benign frequently multiply. The proper epithelial type occurs sin-
or malignant, neoplastic or non-neoplastic, and epithelial gly, measures ≥ 10 mm, is papillated to lobulated, and shows
or non-epithelial. In daily clinical practice, benign lesions relative internal uniformity. If accompanied by cholesterolo-
measuring < 2 cm are usually detected [7]. Most gallbladder sis, internal punctiform echogenic foci are observed, which
polyps are asymptomatic and discovered incidentally during complicates differentiation from cholesterol polyps (Fig. 9).
medical or comprehensive health examinations. The preva- C. Inflammatory, fibrous, and granulomatous polyps:
lence rate is reported to be within 4.2–9.5% in East Asia Whether to treat inflammatory, fibrous, and granulomatous
[8–11] and 3–7% in Western countries [12]. polyps as distinct or similar remains controversial. Inflam-
The main types of gallbladder polyp are as follows: matory polyps are relatively rare, comprising 1.4–12% of
A. Cholesterol polyps: These are the most common gallbladder polyps [15–18]. These polyps, which result from
gallbladder polyps and comprise 62.8% of all gallbladder hyperplasia of edematous loose connective tissues, are inter-
polyps. Although multiple polyps measuring ≤ 10 mm are nally hypoechoic and occasionally accompanied by inflam-
highly likely to be cholesterol polyps, [5] caution is nec- matory thickening of the gallbladder wall.
essary as 5% of polyps are cancerous even if they meas- The characteristic EUS findings are internal anechoic
ure ≤ 10 mm [13]. The characteristic findings on EUS are a spots with hyperechoic polyp surface borders. These find-
deeply notched granular surface and morular morphology. ings appear to occur because of the difference in the acoustic
The internal echo is rough or granular, and highly echogenic features between the single surface layer of the columnar
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epithelium and the edematous stroma [19] (Fig. 10). Fibrous enlarged neoplastic glandular ducts observed as multiple
polyps are made up of connective tissue composed of fibro- microcystic spaces [20] (Fig. 12). Papillary adenomas are
blasts, fibrocytes, and collagen fibers, and imaging findings predominantly of the proper epithelial type with a low solid
resemble those of inflammatory polyps (Fig. 11). Granu- echo and must be differentiated from hyperplastic polyps.
lomatous polyps, which are formed from inflammatory Differentiation between adenomas and adenocarcinomas
granulation tissue, lack a surface epithelium and have a high based on imaging is considered difficult.
rate of comorbidity with acute cholecystitis and gallstones. B. Gallbladder carcinoma (protuberant type): Gall-
bladder carcinoma is considered in cases of diffuse or
ii) Neoplastic lesions localized irregular thickening of the gallbladder wall in
which an irregular mucous membrane surface and a loss
A. Adenomas: Adenomas are classified as tubular or pap- of uniformity in the inner hypoechoic layer are observed.
illary. Tubular adenomas, of which pyloric adenomas are Ultrasound imaging findings are classified as protuberant
common, are pedunculated to subpedunculated and oval. (peduncular/sessile), wall thickening, or both types. Of
The features on EUS are a relatively smooth or nodular the protuberant type, peduncular lesions (type Ip) often
surface, solid internal echogenicity, and the presence of
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is to confirm the presence of cystic anechoic spots reflecting irregular thickening of the gallbladder wall and fibrosis.
RAS inside the thickened wall. Comet tail artifacts are also As the inflammation occasionally affects surrounding
occasionally observed owing to multipath reflection from organs such as the liver and transverse colon, differentia-
RAS or intramural calculi. tion from gallbladder carcinoma is frequently problematic.
The disease may result from impaction of stones in the
ii) Xanthogranulomatous cholecystitis neck of the gallbladder or biliary leakage into the gallblad-
der wall owing to RAS rupture or mucosal ulceration. In
Xanthogranulomatous cholecystitis is a unique form of cases without lithiasis, gallbladder carcinoma may be a
cholecystitis in which the gallbladder wall thickening possible cause. Differentiation between benign and malig-
primarily involves the SS layer and is accompanied by nant types based on EUS alone is frequently difficult.
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iii) Hyperplasia of the gallbladder mucous membrane iv) Gallbladder carcinoma (wall‑thickening type)
accompanying anomalous pancreaticobiliary junction
In the wall-thickening type, differentiation from gallblad-
As an anomalous pancreaticobiliary junction leads to der adenomyomatosis and chronic cholecystitis is problem-
reflux of pancreatic juice into the biliary tract, hyperplas- atic, but in gallbladder carcinoma, the mucous membrane is
tic changes arise in the gallbladder mucous membrane irregular or papillated, thickened areas do not have uniform
(Fig. 16). Hyperplasia of the gallbladder mucous mem- thickness, and the layered structure is ill-defined. Further-
brane is recognized in 38–63% of patients with an anoma- more, microcysts and comet tail artifacts reflecting RAS are
lous pancreaticobiliary junction, with an even higher rate usually not observed (Fig. 17).
of 90–100% particularly in patients without bile duct dila-
tation [21, 22]. 6. EUS‑FNA for gallbladder lesions
In hyperplasia of the gallbladder mucous membrane,
epithelial height is increased, cellular proliferative activ- Bile duct biopsy is the first choice procedure in the patholog-
ity is accelerated, and a mechanism from hyperplasia to ical diagnosis of gallbladder lesions in which a biliary stric-
dysplasia and carcinoma is speculated. ture is present. However, when a biliary stricture is absent,
it is often necessary to rely on cytological examination of
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bile collected from the gallbladder through the cystic duct, with the use and establishment of EUS-FNA for gallbladder
which makes diagnosis difficult. Cytological examination lesions.
using endoscopic naso-gallbladder drainage does not always
have a high success rate, requires a highly proficient practi- Acknowledgements We thank Dr. Edward Barroga (https://orcid
.org/0000-0002-8920-2607), Medical Editor and Professor of Aca-
tioner, and presents problematic points such as perforation demic Writing at St. Luke’s International University, for editing the
of the cystic duct when using a guidewire [23–25]. manuscript.
Although EUS-FNA is highly useful and widely used for
pancreatic carcinoma and gastrointestinal lesions, the deci- Compliance with ethical standards
sion to use EUS-FNA for biliary tract lesions, particularly
gallbladder carcinoma, should be made with care because of Conflict of interest The authors declare that there are no conflicts of
risks such as biliary fistula and dissemination to membranes. interest.
Regional lymphadenopathy is often noted in unresectable Ethical approval All procedures followed were in accordance with the
advanced gallbladder carcinoma [26]. Considering the risks ethical standards of the responsible committee on human experimenta-
such as invasive biliary fistula, which may affect neighbor- tion (institutional and national) and with the Helsinki Declaration of
ing organs including the liver, and peritoneal dissemination, 1964 and later versions.
aspiration from regional lymph nodes is preferable. Hijioka Informed consent Informed consent was obtained from all patients for
et al. have reported that FNA can be performed in gallblad- being included in the study.
der lesions without compromising diagnostic performance
or safety [26]. Moreover, the diagnostic performance of Open Access This article is licensed under a Creative Commons Attri-
EUS-FNA in gallbladder lesions is high, with a sensitivity, bution 4.0 International License, which permits use, sharing, adapta-
specificity, and diagnostic accuracy of 80–100%, 100%, and tion, distribution and reproduction in any medium or format, as long
83–100%, respectively [26–31]. as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
When directly puncturing the gallbladder wall, despite were made. The images or other third party material in this article are
the care taken to gain stroke distance by tangentially punc- included in the article’s Creative Commons licence, unless indicated
turing the gallbladder wall (Fig. 18), the wall may move otherwise in a credit line to the material. If material is not included in
if the gallbladder lumen remains and puncturing is often the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will
difficult. In cases where lesions have invaded the liver, it is need to obtain permission directly from the copyright holder. To view a
recommended to puncture either the liver parenchyma as the copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
invasion site or the gallbladder wall that is in contact with
the liver parenchyma.
References
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3. Choi JH, Seo DW, Choi JH, et al. Utility of contrast-enhanced cancer (in Japanese with English abstract). Jpn J Gastroenterol.
harmonic EUS in the diagnosis of malignant gallbladder polyps. 1994;91:1062–6.
Gastrointest Endosc. 2013;78:484–93. 20. Akatsu T, Aiura K, Shimazu M, et al. Can endoscopic ultrasonog-
4. Imazu H, Mori N, Tajiri H, et al. Contrast-enhanced harmonic raphy differentiate nonneoplastic from neoplastic gallbladder pol-
endoscopic ultrasonography in the differential diagnosis of gall- yps? Dig Dis Sci. 2006;51:416–21.
bladder wall thickening. Dig Dis Sci. 2014;59:1909–16. 21. Hanada K, Itoh M, Hujii K, et al. Pathology and cellular kinetics
5. Karaosmmanoglu AD, Blake M. Hamartomatous polyp of the of gallbladder with an anomalous junction of pancreaticobiliary
gallbladder with an associated choledochal cyst. J Ultrasound duct. Am J Gastroenterol. 1996;91:1007–111.
Med. 2010;29:1663–6. 22. Tsuchida A, Itoi T, Endo M, et al. Pathological features and surgi-
6. Christensen AH, Ishak KG. Benign tumors and pseudotu- cal outcome of pancreaticobiliary maljunction without dilatation
mors of the gallbladder. Report of 180 cases. Arch Pathol. of the extrahepatic bile duct. Oncol Rep. 2004;11:269–76.
1970;90:423–32. 23. Itoi T, Sofuni A, Itokawa F, et al. Endoscopic transpapillary
7. Park EJ, Lee HS, Lee SH, et al. Association between metabolic gallbladder drainage in patients with acute cholecystitis in
syndrome and gallbladder polyps in healthy Korean adults. J whom percutaneous transhepatic approach is contraindicated
Korean Med Sci. 2013;28:876–80. or anatomically impossible (with video). Gastrointest Endosc.
8. Chen CY, Lu CL, Chang FY, et al. Risk factors for gallblad- 2008;68:455–60.
der polyps in the Chinese population. Am J Gastroenterol. 24. Toyooka N, Takeda T, Amano H, et al. Endoscopic naso-gall-
1997;92:2066–8. bladder drainage in the treatment of acute cholecystitis: alleviates
9. Xu Q, Tao LY, Wu Q, et al. Prevalence of and risk factors for bil- inflammation and fixes operator’s aim during early laparoscopic
iary stones and gallbladder polyps in a large Chinese population. cholecystotomy. J Hepatobiliary Pancreat Surg. 2006;13:80–5.
HPB. 2012;14:373–81. 25. Mutigeni M, Iacopini F, Perri V, et al. Endoscopic gallbladder
10. Inui K, Yoshino J, Miyoshi H. Diagnosis of gallbladder tumors. drainage for acute cholecystitis: technical and clinical results.
Intern Med. 2011;50:1133–6. Endoscopy. 2009;41:539–46.
11. Lin WR, Lin DY, Tai DI, et al. Prevalence of and risk factors for 26. Hijioka S, Hara K, Mizuno N, et al. Diagnostic yield of endo-
gall bladder polyps detected by ultrasonography among healthy scopic retrograde cholangiography and of EUS-guided fine needle
Chinese: analysis of 34669 cases. J Gastroenterol Hepatol. aspiration sampling in gallbladder carcinomas. J Hepatobiliary
2008;23:965–9. Pancreat Sci. 2012;19:650–5.
12. Ahrendt SA, Pitt HA. Sabiston textbook of surgery. 17th ed. Phila- 27. Jacobson B, Pitman M, Brugge W. EUS-guided FNA for the diag-
delphia: Elsevier Saunders; 2004. p. 1597–1641. nosis of gallbladder masses. Gastrointest Endosc. 2003;57:251–4.
13. Okada K, Kijima H, Imaizumi T, et al. Wall-invasion pattern cor- 28. Varadarajulu S, Eloubeidi M. Endoscopic ultrasound-guided fine-
relates with survival of patients with gallbladder adenocarcinoma. needle aspiration in the evaluation of gallbladder masses. Endos-
Anticancer Res. 2009;29:685–91. copy. 2005;37:751–4.
14. Azuma T, Yoshikawa T, Araida T, et al. Differential diagnosis of 29. Meara R, Jhala D, Eloubeidi M, et al. Endoscopic ultrasound-
polypoid lesions of the gallbladder by endoscopic ultrasonogra- guided FNA biopsy of bile duct and gallbladder: analysis of 53
phy. Am J Surg. 2001;81:65–70. cases. Cytopathology. 2006;17:42–9.
15. Kubota K, Bandai Y, Makuuchi M, et al. How should polypoid 30. Hijioka S, Mekky MA, Bhatia V, et al. Can EUS-guided FNA
lesions of the gallbladder be treated in the era of laparoscopic distinguish between gallbladder cancer and xanthogranulomatous
cholecystectomy? Surgery. 1995;117:481–7. cholecystitis? Gastrointest Endosc. 2010;72:622–7.
16. Terzi C, Sökmen S, Ugurlu M, et al. Polypoid lesions of the gall- 31. Ogura T, Kurisu Y, Masuda D, et al. Can endoscopic ultrasound-
bladder: report of 100 cases with special reference to operative guided fine needle aspiration offer clinical benefit for thick-walled
indications. Surgery. 2000;127:622–7. gallbladders? Dig Dis Sci. 2014;59:1917–24.
17. Sadamoto Y, Oda S, Nawata H, et al. A useful approach to the
differential diagnosis of small polypoid lesions of the gallbladder, Publisher’s Note Springer Nature remains neutral with regard to
utilizing an endoscopic ultrasound scoring system. Endoscopy. jurisdictional claims in published maps and institutional affiliations.
2002;34:959–65.
18. Lee KF, Wong J, Li JC, Lai PB. Polypoid lesions of the gallblad-
der. Am J Surg. 2004;188:186–90.
19. Kyokane T, Akita Y, Sato T, et al. A case of inflammatory
polyp of the gallbladder which was difficult to differentiate from
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